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综合基因组学和代谢组学方法从与新加坡海洋样本相关的微生物中发现潜在的抗群体感应天然产物。

Integrated Genomic and Metabolomic Approach to the Discovery of Potential Anti-Quorum Sensing Natural Products from Microbes Associated with Marine Samples from Singapore.

机构信息

Natural Sciences and Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore 637616, Singapore.

p53 Laboratory, Agency for Science, Technology and Research (A*STAR), #06-06, Immunos, 8A Biomedical Grove, Singapore 138648, Singapore.

出版信息

Mar Drugs. 2019 Jan 21;17(1):72. doi: 10.3390/md17010072.

Abstract

With 70% of the Earth's surface covered in water, the marine ecosystem offers immense opportunities for drug discovery and development. Due to the decreasing rate of novel natural product discovery from terrestrial sources in recent years, many researchers are beginning to look seaward for breakthroughs in new therapeutic agents. As part of an ongoing marine drug discovery programme in Singapore, an integrated approach of combining metabolomic and genomic techniques were initiated for uncovering novel anti-quorum sensing molecules from bacteria associated with subtidal samples collected in the Singapore Strait. Based on the culture-dependent method, a total of 102 marine bacteria strains were isolated and the identities of selected strains were established based on their 16S rRNA gene sequences. About 5% of the marine bacterial organic extracts showed quorum sensing inhibitory (QSI) activity in a dose-dependent manner based on the QS reporter system. In addition, the extracts were subjected to mass spectrometry-based molecular networking and the genome of selected strains were analysed for known as well as new biosynthetic gene clusters. This study revealed that using integrated techniques, coupled with biological assays, can provide an effective and rapid prioritization of marine bacterial strains for downstream large-scale culturing for the purpose of isolation and structural elucidation of novel bioactive compounds.

摘要

由于近年来从陆地来源发现新天然产物的速度下降,许多研究人员开始将目光投向海洋,以期在新的治疗剂方面取得突破。作为新加坡正在进行的海洋药物发现计划的一部分,采用了代谢组学和基因组学技术相结合的综合方法,从在新加坡海峡采集的潮间带样本中与细菌相关的物质中发现新型抗群体感应分子。基于培养依赖的方法,共分离出 102 株海洋细菌株,并根据其 16S rRNA 基因序列确定了选定菌株的身份。根据 QS 报告系统,约有 5%的海洋细菌有机提取物具有群体感应抑制(QSI)活性,呈剂量依赖性。此外,还对提取物进行了基于质谱的分子网络分析,并对选定菌株的基因组进行了分析,以寻找已知和新的生物合成基因簇。这项研究表明,使用综合技术,结合生物测定,可以有效地快速确定海洋细菌菌株的优先级,以便进行下游大规模培养,从而分离和阐明新型生物活性化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7fa/6356914/e161851b1c14/marinedrugs-17-00072-g001.jpg

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